Duragesic Mat

In the U.S.

• Duragesic
• Ionsys

In Canada

• Duragesic Mat

Available Dosage Forms:

• Patch, Extended Release
• Patch, Device Assisted

Therapeutic Class: Analgesic

Chemical Class: Opioid

Fentanyl skin patch is used to treat severe pain, including acute pain following surgery. Ionsys® is applied by your healthcare provider in a hospital setting after surgery for the short-term management of acute pain. Duragesic® is used for severe chronic pain when around-the-clock pain relief is needed for a long period of time. Fentanyl is a strong narcotic analgesic (pain medicine). It acts on the central nervous system (CNS) to relieve pain.

The Duragesic® skin patch should not be used if you need pain medicine for just a short time, such as after dental surgery or tonsil surgery. Do not use the patch for mild pain or pain that occurs only once in a while.

When a narcotic medicine is used for a long time, it may become habit-forming, causing mental or physical dependence. However, people who have continuing pain should not let the fear of dependence keep them from using narcotics if needed. Mental dependence (addiction) is not likely to occur when narcotics are used for this purpose. Physical dependence may lead to withdrawal side effects if treatment is stopped suddenly, but the adverse effects can usually be prevented by gradually reducing the dose.

This medicine is available only with your doctor's prescription.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of the Duragesic® patch in children 2 years and older. However, pediatric patients must be opioid-tolerant before using a fentanyl patch. Safety and efficacy have not been established in children younger than 2 years.

Appropriate studies have not been performed on the relationship of age to the effects of the Ionsys® patch in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of fentanyl skin patch in the elderly. However, elderly patients are more likely to have drowsiness and age-related lung, kidney, liver, or heart problems, which may require caution and an adjustment in the dose for patients receiving fentanyl skin patch in order to avoid serious side effects.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Amifampridine
• Mifepristone
• Nalmefene
• Naltrexone
• Safinamide

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acepromazine
• Alefacept
• Alfentanil
• Almotriptan
• Alprazolam
• Amineptine
• Amiodarone
• Amisulpride
• Amitriptyline
• Amitriptylinoxide
• Amobarbital
• Amoxapine
• Amphetamine
• Anileridine
• Aripiprazole
• Asenapine
• Baclofen
• Benperidol
• Benzphetamine
• Blinatumomab
• Boceprevir
• Bromazepam
• Bromopride
• Brompheniramine
• Buprenorphine
• Buspirone
• Butabarbital
• Butorphanol
• Carbamazepine
• Carbinoxamine
• Cariprazine
• Carisoprodol
• Carphenazine
• Ceritinib
• Chloral Hydrate
• Chlordiazepoxide
• Chlorpheniramine
• Chlorpromazine
• Chlorzoxazone
• Citalopram
• Clarithromycin
• Clobazam
• Clomipramine
• Clonazepam
• Clorazepate
• Clozapine
• Cobicistat
• Cocaine
• Codeine
• Conivaptan
• Cyclobenzaprine
• Desipramine
• Desmopressin
• Desvenlafaxine
• Dexmedetomidine
• Dextroamphetamine
• Dextromethorphan
• Dezocine
• Diazepam
• Dibenzepin
• Dichloralphenazone
• Difenoxin
• Dihydrocodeine
• Diphenhydramine
• Diphenoxylate
• Dolasetron
• Donepezil
• Doxepin
• Droperidol
• Duloxetine
• Eletriptan
• Eluxadoline
• Enflurane
• Enzalutamide
• Escitalopram
• Estazolam
• Eszopiclone
• Ethchlorvynol
• Ethopropazine
• Ethylmorphine
• Flibanserin
• Fluoxetine
• Fluphenazine
• Flurazepam
• Fluspirilene
• Fluvoxamine
• Fosphenytoin
• Fospropofol
• Frovatriptan
• Furazolidone
• Golimumab
• Granisetron
• Guselkumab
• Halazepam
• Haloperidol
• Halothane
• Hexobarbital
• Hydrocodone
• Hydromorphone
• Hydroxytryptophan
• Hydroxyzine
• Idelalisib
• Imipramine
• Indinavir
• Iproniazid
• Isocarboxazid
• Isoflurane
• Itraconazole
• Ketamine
• Ketobemidone
• Ketoconazole
• Levomilnacipran
• Levorphanol
• Linezolid
• Lisdexamfetamine
• Lithium
• Lofepramine
• Lopinavir
• Lorazepam
• Lorcaserin
• Loxapine
• Lumacaftor
• Meclizine
• Melitracen
• Melperone
• Meperidine
• Mephobarbital
• Meprobamate
• Meptazinol
• Mesoridazine
• Metaxalone
• Methadone
• Methamphetamine
• Methdilazine
• Methocarbamol
• Methohexital
• Methotrimeprazine
• Methylene Blue
• Midazolam
• Milnacipran
• Mirtazapine
• Mitotane
• Moclobemide
• Molindone
• Moricizine
• Morphine
• Morphine Sulfate Liposome
• Nalbuphine
• Naratriptan
• Nefazodone
• Nelfinavir
• Netupitant
• Nialamide
• Nicardipine
• Nicomorphine
• Nifedipine
• Nitrazepam
• Nitrous Oxide
• Nortriptyline
• Olanzapine
• Ondansetron
• Opipramol
• Opium
• Opium Alkaloids
• Orphenadrine
• Oxazepam
• Oxycodone
• Oxymorphone
• Palonosetron
• Papaveretum
• Paregoric
• Paroxetine
• Pazopanib
• Pentazocine
• Pentobarbital
• Perampanel
• Perazine
• Periciazine
• Perphenazine
• Phenelzine
• Phenobarbital
• Phenytoin
• Pimozide
• Piperacetazine
• Pipotiazine
• Piritramide
• Pitolisant
• Posaconazole
• Prazepam
• Primidone
• Procarbazine
• Prochlorperazine
• Promazine
• Promethazine
• Propofol
• Protriptyline
• Quazepam
• Quetiapine
• Ramelteon
• Ranolazine
• Rasagiline
• Remifentanil
• Remoxipride
• Ribociclib
• Rifampin
• Ritonavir
• Rizatriptan
• Saquinavir
• Secobarbital
• Secukinumab
• Selegiline
• Sertindole
• Sertraline
• Sibutramine
• Sodium Oxybate
• St John's Wort
• Sufentanil
• Sulpiride
• Sumatriptan
• Suvorexant
• Tapentadol
• Telaprevir
• Telithromycin
• Temazepam
• Thiethylperazine
• Thiopental
• Thiopropazate
• Thioridazine
• Tianeptine
• Tilidine
• Tizanidine
• Tolonium Chloride
• Topiramate
• Tramadol
• Tranylcypromine
• Trazodone
• Triazolam
• Trifluoperazine
• Trifluperidol
• Triflupromazine
• Trimeprazine
• Trimipramine
• Tryptophan
• Venlafaxine
• Vilazodone
• Voriconazole
• Vortioxetine
• Zaleplon
• Ziprasidone
• Zolmitriptan
• Zolpidem
• Zopiclone
• Zotepine

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Alcohol abuse, or history of or
• Brain tumor, history of or
• Breathing problems (eg, asthma, apnea, low oxygen levels) or
• Chronic obstructive pulmonary disease (COPD) or
• Cor pulmonale (serious heart condition) or
• Gallbladder disease (eg, gallstones) or
• Depression, history of or
• Drug dependence, including narcotic or illicit drug abuse or dependence, history of or
• Head injury, history of or
• Mental health problems, history of or
• Weakened physical condition—Use with caution. May increase risk for more serious side effects.

• Bradyarrhythmia (slow heart rhythm) or
• Hypotension (low blood pressure) or
• Pancreatitis (inflammation of the pancreas), acute or
• Seizures, history of—Use with caution. May make these conditions worse.

• Kidney disease or
• Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

• Stomach or bowel blockage (eg, paralytic ileus), known or suspected—Should not be used in patients with this condition.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Decrease in the amount of urine or in the frequency of urination
• seeing, hearing, or feeling things that are not there

• Chest pain
• difficulty with speaking
• fainting
• mood or mental changes
• problems with walking
• redness, swelling, itching, or bumps on the skin at the place of application
• spitting blood

• Bloating or swelling of the face, hands, lower legs, or feet
• fast or pounding heartbeat or pulse
• rapid weight gain

Get emergency help immediately if any of the following symptoms of overdose occur:

• Cold, clammy skin
• convulsions (seizures)
• drowsiness that is so severe you are not able to answer when spoken to or, if asleep, cannot be awakened
• pinpoint (small) pupils in the eyes
• slow heartbeat
• very slow or troubled breathing

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Abdominal or stomach pain that was not present before treatment
• confusion
• constipation
• diarrhea
• dizziness, drowsiness, or lightheadedness
• false sense of well-being
• feeling anxious
• headache
• indigestion
• loss of appetite
• nausea or vomiting
• sweating
• weakness

• Feeling anxious and restless at the same time
• feeling of crawling, tingling, or burning of the skin
• memory loss
• unusual dreams

• Change or problem with discharge of semen
• decreased interest in sexual intercourse
• inability to have or keep an erection
• loss in sexual ability, desire, drive, or performance
• not able to have an orgasm
• weight loss

After you stop using this medicine, it may still produce some side effects that need attention. During this period of time, check with your doctor immediately if you notice the following side effects:

• Body aches
• fast heartbeat
• fever, runny nose, or sneezing
• gooseflesh feeling
• increased sweating
• increased yawning
• nervousness, restlessness, or irritability
• shivering or trembling
• stomach cramps
• trouble sleeping
• unusually large pupils in the eyes

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

You should not receive this medicine if you are allergic to fentanyl or other narcotic pain medicines.

It is very important that you are monitored closely by your doctor when receiving fentanyl injection. This will allow your doctor to determine whether it is working properly and if you should continue to receive treatment.

Check with your doctor right away if you or your child have bluish lips or skin; chest pain; difficulty with breathing; a fast, pounding or irregular heartbeat or pulse; shortness of breath; or muscle stiffness after receiving fentanyl.

MISUSE OF NARCOTIC MEDICATION CAN CAUSE ADDICTION, OVERDOSE, OR DEATH, especially in a child or other person using the medicine without a prescription.

Fentanyl is injected into a muscle, or into a vein through an IV. A healthcare provider will give you this injection as part of the anesthesia given for your surgery or medical procedure.

Your breathing, blood pressure, oxygen levels, and other vital signs will be watched closely while you are receiving fentanyl.

You may be given other pain medications to use after your fentanyl treatment is discontinued.

Applies to fentanyl: film, lozenge/troche, spray, tablet

Other dosage forms:

• injection injectable, injection solution
• nasal spray
• transdermal patch device assisted, transdermal patch extended release

Along with its needed effects, fentanyl may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking fentanyl:

• Black, tarry stools
• blurred vision
• chest pain
• confusion
• convulsions
• cough
• decreased urine
• difficult or labored breathing
• dizziness
• dry mouth
• fainting
• fever or chills
• increased thirst
• irregular heartbeat
• lightheadedness
• loss of appetite
• lower back or side pain
• mood changes
• muscle pain or cramps
• nausea or vomiting
• nervousness
• numbness or tingling in the hands, feet, or lips
• painful or difficult urination
• pale skin
• pounding in the ears
• rapid breathing
• sneezing
• sore throat
• sunken eyes
• swelling of the hands, ankles, feet, or lower legs
• tightness in the chest
• troubled breathing with exertion
• ulcers, sores, or white spots in the mouth
• unusual bleeding or bruising
• unusual tiredness or weakness
• wrinkled skin

• Abdominal or stomach pain
• change in walking and balance
• clumsiness or unsteadiness
• decreased awareness or responsiveness
• decreased frequency of urination
• headache
• muscle twitching or jerking
• pounding in the ears
• rhythmic movement of the muscles
• seeing, hearing, or feeling things that are not there
• seizures
• severe constipation
• severe sleepiness
• shakiness in the legs, arms, hands, or feet
• slow or fast heartbeat
• thinking abnormalities
• trembling or shaking of the hands or feet

Get emergency help immediately if any of the following symptoms of overdose occur while taking fentanyl:

• Extremely shallow or slow breathing

Some side effects of fentanyl may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Back pain
• diarrhea
• difficulty having a bowel movement (stool)
• difficulty with moving
• discouragement
• feeling sad or empty
• irritability
• lack or loss of strength
• loss of interest or pleasure
• muscle stiffness
• pain in the joints
• sleepiness or unusual drowsiness
• tiredness
• trouble concentrating
• trouble sleeping
• weight loss

• Changes in vision
• excessive muscle tone
• feeling of constant movement of self or surroundings
• feeling of warmth or heat
• flushing or redness of the skin, especially on the face and neck
• irritation, pain, or sores at the site of application
• itching skin
• muscle tension or tightness
• rash
• sensation of spinning
• sweating

• Tooth pain
• trouble with gums
• trouble with teeth

Applies to fentanyl: buccal film, buccal tablet, compounding powder, injectable solution, intravenous solution, nasal spray, oral lozenge, oral transmucosal lozenge, sublingual spray, sublingual tablet, transdermal device, transdermal film extended release

General

The most commonly reported adverse reactions included headache, nausea, vomiting, ,dizziness, and constipation.[Ref]

Nervous system

Very common (10% or more): Somnolence, dizziness
Common (1% to 10%): Sedation, pyrexia, fatigue, lethargy, tremor, headache, chills, irritability, malaise, confusion, abnormal thinking, anxiety, dysphoria
Uncommon (0.1% to 1%): Hyperesthesia
Very rare (less than 0.01%): Severe hemiplegic migraine
Frequency not reported: Slurred speech, paresthesia, hypesthesia, tremor
Postmarketing reports: Loss of consciousness, vertigo, coma, shock, convulsion[Ref]

Cases of seizures have occasionally been reported, but some investigators have suggested that the seizure-like events reported may have been episodes of fentanyl induced-rigidity.[Ref]

Cardiovascular

One report has suggested that epidural fentanyl may mask the pain of myocardial ischemia in patients treated with fentanyl for other reasons. Another report has suggested that QTc interval prolongation may occur in some patients receiving the related narcotic sufentanil. Another report has implicated fentanyl as a potential cause of pulsus alternans in a patient with aortic stenosis and congestive heart failure.

Nevertheless, fentanyl has been advocated by some as a satisfactory agent for coronary artery surgery.[Ref]

Common (1% to 10%): Tachycardia
Uncommon (0.1% to 1%): Sinus tachycardia, chest pain, hypertension, hypotension, palpitations
Rare (less than 0.1%): Arrhythmias, cardiac arrest
Frequency not reported: Syncope, vasodilation, bradycardia, bigeminy, myocardial infarct
Postmarketing reports: Circulatory depression[Ref]

Gastrointestinal

Very common (10% or more): Nausea (18%), vomiting (10%), constipation
Common (1% to 10%): Dry mouth, abdominal distension, gastritis, dysphagia, dyspepsia, gastroesophageal reflux disease, ascites, hematemesis, taste perversion, abdominal pain, dehydration, anorexia, cachexia, vomiting, dry mouth, mouth ulcers/stomatitis, tongue edema
Uncommon (0.1% to 1%): Abdomen enlarged, flatulence
Rare (less than 0.1%): Choledochoduodenal sphincter spasm
Frequency not reported: Diarrhea
Postmarketing reports: Ileus, dental caries, tooth loss, gingival recession, gingivitis, gingival bleeding, lip edema, pharyngeal edema, gum bleeding, ulcer[Ref]

Genitourinary

Uncommon (0.1% to 1%): Urinary retention
Very rare (less than 0.01%): Priapism
Frequency not reported: Urinary tract infection, urination impaired, hematuria, urinary urgency, dysuria[Ref]

Dermatologic

Approximately 60% of patients had some redness at the skin site 24-hours after removal of the iontophoretic transdermal system. The majority of skin events were categorized as mild, erythema and papules were observed; 2 patients had hyperpigmentation at the application site lasting 2 to 3 weeks; 3 patients had a rectangular mark at the application site which persisted for up to 3 months.[Ref]

Very common(10% or more): Iontophoretic transdermal system: Application site reaction-Erythema (14%)
Common (1% to 10%): Application site irritation, pruritus
Uncommon (0.1% to 1%): Hyperhidrosis, rash
Rare (less than 0.1%): Systemic rashes
Frequency not reported: vesicles, papules/pustules, dry and flaky skin, vesiculobullous rash wound site oozing/bleeding, wound site inflammation/erythema
Postmarketing reports: Application site discharge, application site bleeding, application site infection, rash and scab, erosion, hyperesthesia, application site necrosis[Ref]

Hypersensitivity

Rare (less than 0.1%): Anaphylaxis[Ref]

Hematologic

The hemolysis observed may have been related to rapid injection of large volumes of hypotonic fentanyl solution. The authors therefore recommend slower injection rates and/or mixture in isotonic fluid.[Ref]

Common (1% to 10%): Anemia, neutropenia, lymphadenopathy, thrombocytopenia, leukopenia, aspartate aminotransferase increased, blood alkaline phosphatase increased, blood glucose increased, blood lactate increased, hypoalbuminemia, vasodilation[Ref]

Immunologic

Uncommon (0.1% to 1%): Oral candidiasis, cellulitis, pneumonia, urinary tract infection, oral herpes, gastroenteritis, laryngitis
Very rare (less than 0.01%): Recurrent herpes simplex infection following epidural administration[Ref]

Metabolic

Common (1% to 10%): Asthenia, peripheral edema, weight decreased, hypokalemia, hyponatremia, hypocalcemia
Very rare (less than 0.01%): Syndrome of inappropriate antidiuretic hormone
Frequency not reported: abnormal healing, dehydration[Ref]

Endocrine

Uncommon (0.1% to 1%): Hot flush[Ref]

Musculoskeletal

Common (1% to 10%): Fall/accidental injury, back pain, arthralgia, joint swelling, muscular weakness, myoclonus, involuntary muscle contractions, muscle rigidity (involving the respiratory musculature including the glottis)
Frequency not reported: Leg cramps, myalgia
Postmarketing reports: Abnormal gait/incoordination[Ref]

Ocular

Uncommon (0.1% to 1%): Vision blurred, dry eye
Rare (less than 0.1%): Abnormal vision[Ref]

Psychiatric

Common (1% to 10%): Depression, confusional state, hallucination, insomnia
Uncommon (0.1% to 1%): Anxiety, agitation, restlessness, agitation, disorientation, abnormal dreams, depersonalization, depression, emotional lability, euphoria, delirium
Frequency not reported: Nervousness[Ref]

Respiratory

Common (1% to 10%): Dyspnea, rhinitis, yawning, respiratory distress, apnea, bradypnea, hypoventilation, respiratory depression
Uncommon (0.1% to 1%): Cough, increased bronchial secretion, dysphonia, pharyngolaryngeal pain, wheezing, hypoxia, exertional dyspnea
Very rare (less than 0.01%): Acute noncardiogenic pulmonary edema
Frequency not reported: Asthma, hiccup, atelectasis, hyperventilation
Postmarketing reports: Respiratory arrest[Ref]

Some side effects of fentanyl may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Doses should be titrated to appropriate effects; wide range of doses exist, dependent upon desired degree of analgesia/anesthesia, clinical environment, patient's status, and presence of opioid tolerance.

Neonates: Analgesia: International Evidence-Based Group for Neonatal Pain recommendations:
Intermittent doses: Slow IV push: 0.5 to 3 mcg/kg/dose
---Continuous IV infusion: 0.5 to 2 mcg/kg/hour
---Sedation/analgesia: Slow IV push: 1 to 4 mcg/kg/dose; may repeat every 2 to 4 hours
---Continuous sedation/analgesia: Initial IV bolus: 1 to 2 mcg/kg, then 0.5 to 1 mcg/kg/hour; titrate upward
---Mean required dose: Neonates with gestational age less than 34 weeks: 0.64 mcg/kg/hour; neonates with gestational age greater than or equal to 34 weeks: 0.75 mcg/kg/hour
---Continuous sedation/analgesia during extracorporeal membrane oxygenation (ECMO): Initial IV bolus: 5 to 10 mcg/kg slow IV push over 10 minutes, then 1 to 5 mcg/kg/hour; titrate upward; tolerance may develop; higher doses (up to 20 mcg/kg/hour) may be needed by day 6 of ECMO.

Younger infants:
---Sedation/analgesia: Slow IV push: 1 to 4 mcg/kg/dose; may repeat every 2 to 4 hours
---Continuous sedation/analgesia: Initial IV bolus: 1 to 2 mcg/kg, then 0.5 to 1 mcg/kg/hour; titrate upward
---Continuous sedation/analgesia during extracorporeal membrane oxygenation ECMO: Initial IV bolus: 5 to 10 mcg/kg slow IV push over 10 minutes, then 1 to 5 mcg/kg/hour; titrate upward; tolerance may develop; higher doses (up to 20 mcg/kg/hour) may be needed by day 6 of ECMO.

Older Infants and Children 1 to 12 years:
---Sedation for minor procedures/analgesia: IM or IV: 1 to 2 mcg/kg/dose; may repeat at 30 to 60 minute intervals. Note: Children 18 to 36 months of age may require 2 to 3 mcg/kg/dose.
--- Intranasal: Children greater than or equal to 10 kg: 1.5 mcg/kg once (maximum: 100 mcg/dose); reported range: 1 to 2 mcg/kg; some studies allowed for additional incremental doses of 0.5 mcg/kg to be administered every 5 minutes, not to exceed a total dose of 3 mcg/kg depending on pain type and severity.
---Continuous sedation/analgesia: Initial IV bolus: 1 to 2 mcg/kg then 1 mcg/kg/hour; titrate upward; usual: 1 to 3 mcg/kg/hour; some require 5 mcg/kg/hour
---Moderate to severe chronic pain: Transdermal patch: Opioid-tolerant children greater than or equal to 2 years receiving at least 60 mg oral morphine equivalents per day: Initial: 25 mcg/hour system or higher, based on conversion to fentanyl equivalents and administration of equianalgesic dosage (see package insert for further information); use short-acting analgesics for first 24 hours with supplemental PRN doses thereafter (for breakthrough pain); dose may be increased after 3 days, based on the daily dose of supplementary PRN opioids required; use the ratio of 45 mg of oral morphine equivalents per day to a 12.5 mcg/hour increase in transdermal patch dosage; change patch every 72 hours; Note: Dosing intervals less than every 72 hours are not recommended for children and adolescents. Initiation of the transdermal patch in children taking less than 60 mg of oral morphine equivalents per day has not been studied in controlled clinical trials; in open-label trials, children 2 to 18 years of age who were receiving at least 45 mg of oral morphine equivalents per day were started with an initial transdermal dose of 25 mcg/hour (or higher, depending upon equianalgesic dose of opioid received).

Children greater than or equal to 5 years and less than 50 kg:
Patient-controlled analgesia (PCA): IV: Opioid-naive: Note: PCA has been used in children as young as 5 years of age; however, clinicians need to assess children 5 to 8 years of age to determine if they are able to use the PCA device correctly. All patients should receive an initial loading dose of an analgesic (to attain adequate control of pain) before starting PCA for maintenance. Adjust doses, lockouts, and limits based on required loading dose, age, state of health, and presence of opioid tolerance. Use lower end of dosing range for opioid-naive. Assess patient and pain control at regular intervals and adjust settings if needed.

Usual concentration: Determined by weight; some clinicians use the following:
---Children less than 12 kg: 10 mcg/mL
---Children 12 to 30 kg: 25 mcg/mL
---Children greater than 30 kg: 50 mcg/mL
---Demand dose: Usual initial: 0.5 to 1 mcg/kg/dose; usual range: 0.5 to 1 mcg/kg/dose
---Lockout: Usual initial: 5 doses/hour
---Lockout interval: Range: 6 to 8 minutes
---Usual basal rate: 0 to 0.5 mcg/kg/hour

Children greater than 12 years to adult:
Sedation for minor procedures/analgesia: IV: 0.5 to 1 mcg/kg/dose; may repeat after 30 to 60 minutes; or 25 to 50 mcg, repeat full dose in 5 minutes if needed, may repeat 4 to 5 times with 25 mcg at 5 minute intervals if needed. Note: Higher doses are used for major procedures.

Continuous sedation/analgesia:
---Less than 50 kg: Initial IV bolus: 1 to 2 mcg/kg; continuous infusion rate: 1 to 2 mcg/kg/hour
---Greater than 50 kg: Initial IV bolus: 1 to 2 mcg/kg or 25 to 100 mcg/dose; continuous infusion rate: 1 to 2 mcg/kg/hour or 25 to 200 mcg/hour

Patient-controlled analgesia (PCA): IV: Children greater than 50 kg, Adolescents greater than 50 kg, and Adults: Note: All patients should receive an initial loading dose of an analgesic (to attain adequate control of pain) before starting PCA for maintenance. Adjust doses, lockouts, and limits based on required loading dose, age, state of health, and presence of opioid tolerance. Use lower end of dosing range for opioid-naive. Assess patient and pain control at regular intervals and adjust settings if needed:

---Usual concentration: 50 mcg/mL
---Demand dose: Usual initial: 20 mcg; usual range: 10 to 50 mcg
---Lockout interval: Usual initial: 6 minutes; usual range: 5 to 8 minutes
---Usual basal rate: less than or equal to 50 mcg/hour

Preoperative sedation, adjunct to regional anesthesia, postoperative pain: IM, IV: 25 to 100 mcg/dose

Adjunct to general anesthesia: Slow IV:
---Low dose: 0.5 to 2 mcg/kg/dose depending on the indication
---Moderate dose: Initial: 2 to 20 mcg/kg/dose; Maintenance (bolus or infusion): 1 to 2 mcg/kg/hour. Discontinuing fentanyl infusion 30 to 60 minutes prior to the end of surgery will usually allow adequate ventilation upon emergence from anesthesia. For "fast-tracking" and early extubation following major surgery, total fentanyl doses are limited to 10 to 15 mcg/kg.
---High dose: 20 to 50 mcg/kg/dose; Note: High dose fentanyl as an adjunct to general anesthesia is rarely used, but is still described in the manufacturer label.

General anesthesia without additional anesthetic agents: IV: 50 to 100 mcg/kg with oxygen and skeletal muscle relaxant

Moderate to severe chronic pain: Transdermal patch: Opioid tolerant patients receiving at least 60 mg oral morphine equivalents per day: Initial: 25 mcg/hour system or higher, based on conversion to fentanyl equivalents and administration of equianalgesic dosage (see package insert for further information); use short-acting analgesics for first 24 hours with supplemental PRN doses thereafter (for breakthrough pain); dose may be increased after 3 days based on the daily dose of supplementary PRN opioids required; use the ratio of 45 mg of oral morphine equivalents per day to a 12.5 mcg/hour increase in transdermal patch dosage; transdermal patch is usually administered every 72 hours but select adult patients may require every 48-hour administration; dosage increase administered every 72 hours should be tried before 48-hour schedule is used.

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for:
-Fentanyl Iontophoretic Transdermal System (Ionsys(R)); it includes elements to assure safe use and an implementation system.
-Transmucosal Immediate-Release Fentanyl Products (sublingual tablets, oral lozenges, buccal tablets, nasal spray, and sublingual spray); it includes a medication guide, elements to assure safe use, and an implementation system.
-Transdermal Fentanyl Systems (shared system for extended-release and long-acting opioid analgesics); it includes a medication guide and elements to assure safe use.
Additional information is available at www.fda.gov/REMS

US BOXED WARNINGS: Iontophoretic Transdermal Systems
- LIFE-THREATENING RESPIRATORY DEPRESSION; Use may result in potentially life-threatening respiratory depression and death as a result of the active drug fentanyl. Only the patient should activate dosing. Accidental exposure to an intact transdermal system or to the hydrogel component, especially by children, through contact with skin or contact with mucous membranes, can result in a fatal overdose of fentanyl. This system is only for use in hospitalized patients; treatment should be discontinued before patient leaves the hospital.
-ADDICTION, ABUSE, and MISUSE: This drug exposes users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing and monitor regularly for the development of these behaviors or conditions.
ACCIDENTAL EXPOSURE: Because of the risk of life-threatening respiratory depression resulting from accidental exposure, this drug is available only through a restricted REMS program.
-CYP450 3A4 INTERACTION: Concomitant use with CYP450 3A4 inhibitors may result in an increase in fentanyl plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. Additionally, discontinuation of a concomitantly used CYP450 3A4 inducer may result in an increase in fentanyl plasma concentrations. Monitor patients concomitantly receiving any CYP450 3A4 inhibitor or inducer.

US BOXED WARNINGS: Transmucosal Immediate-Release Fentanyl (TIRF) Products (sublingual and buccal tablets, transmucosal lozenges, nasal and sublingual spray)
-RESPIRATORY DEPRESSION: Fatal respiratory depression has occurred in patients treated with immediate-release transmucosal fentanyl, including following used in opioid non-tolerant patients and improper dosing. The interchange of one TIRF product for any other fentanyl product may result in fatal overdose. Due to the risk of respiratory depression, TIRF products are contraindicated in the management of acute or postoperative pain including headache/migraine and in opioid non-tolerant patients. Keep out of reach of children. Concomitant use with CYP450 3A4 inhibitors may result in an increase in fentanyl plasma concentrations, and may cause potentially fatal respiratory depression.
-MEDICATION ERRORS: Substantial differences exist in the pharmacokinetic profile of fentanyl products that may result in clinically important differences in the extent of absorption and possible fatal overdose. When prescribing, do not convert patients on a mcg per mcg basis; when dispensing, do not substitute TIRF for each other or other fentanyl products.
-ABUSE POTENTIAL: Fentanyl is a schedule II controlled substance, with an abuse liability similar to other opioid analgesics, legal or illicit. Physicians or pharmacists should consider the risk of misuse, abuse or diversion when prescribing or dispensing. Healthcare professionals who prescribe to outpatients, pharmacies, and distributors must enroll in the TIRF REMS Access program.

US BOXED WARNINGS: Transdermal Systems
-ADDICTION, ABUSE, and MISUSE: The drug exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing and monitor regularly for the development of these behaviors or conditions.
-LIFE-THREATENING RESPIRATORY DEPRESSION: Serious, life-threatening, or fatal respiratory depression may occur, even when used as recommended. Monitor for respiratory depression, especially during initiation and following dose increases. Because of the risk of respiratory depression, this drug is contraindicated for use as an as-needed analgesic, in non-opioid tolerant patients, in acute pain, and in postoperative pain.
-ACCIDENTAL EXPOSURE: Deaths due to fatal overdose of this drug have occurred due to accidental exposure. Strict adherence to the recommended handling and disposal instructions is of the utmost importance to prevent accidental exposure.
-NEONATAL OPIOID WITHDRAWAL SYNDROME: Prolonged use of this drug during pregnancy may result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
-CYP450 3A4 INTERACTION: Concomitant use with CYP450 3A4 inhibitors may result in an increase in fentanyl plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. Additionally, discontinuation of a concomitantly used CYP450 3A4 inducer may result in an increase in fentanyl plasma concentrations. Monitor all patients concomitantly receiving any CYP450 3A4 inhibitor or inducer.
-HEAT EXPOSURE: Exposure of the application site and surrounding area to direct external heat sources, such as heating pads or electric blankets, heat or tanning lamps, sunbathing, hot baths, saunas, hot tubs, and heated water beds may increase drug absorption and has resulted in fatal overdose and death. Patients wearing transdermal systems who develop fever or increased core body temperature due to strenuous exertion are also at risk for increased drug exposure and may require dose adjustment to avoid overdose and death.

-Iontophoretic transdermal system, Buccal tablets, Nasal spray, and Sublingual tablets and spray: Safety and efficacy have not been established in patients younger than 18 years.
-Oral transmucosal lozenge: Safety and efficacy have not been established in patients younger than 16 years.
-Parenteral and Transdermal systems: Safety and efficacy have not been established in patients younger than 2 years.

Consult WARNINGS section for additional precautions.

US Controlled Substance: Schedule II